Angioplasty and the delivery of therapeutic agent to the interior lumen walls are common medical practices in the treatment of stenosis and restenosis. Stenosis is a condition in which a region of a blood vessel has been narrowed to such a degree that blood flow is restricted. If the stenosis is severe, treatment is required to restore adequate blood flow. Despite treatment, in time, the site may undergo restenosis. Restenosis may occur because the treatment procedure sometimes creates cracks in plaque on the vessel wall which leave jagged surfaces that can induce blood clotting at the site. Another cause of restenosis is the development of intimal proliferation. This condition is characterized by excessive cell growth that is triggered by the trauma of the treatment.
Angioplasty involves the insertion of a catheter, e.g., a balloon catheter, into a blood vessel to expand an occluded region of the blood vessel, and is frequently used to treat arteriosclerosis. The balloon is inflated, often by injecting a suitable fluid into the balloon, at the site to widen the lumen and then deflated and removed from the body. Angioplasty has become a successful alternative to coronary arterial bypass surgery. The occluded area is compressed radially outward to increase the cross-sectional area of the artery so that the artery has an acceptable blood flow rate.
The delivery of therapeutic agent to the interior lumen walls of a diseased vessel can be useful in treating stenosis or restenosis. The delivery of the therapeutic agent can be completed through the use of numerous devices and/or procedures including direct injection by syringe and needle, pneumatic injection of the therapeutic agent into the diseased tissue, and the release of the therapeutic agent, near the target site, by the distal end of a catheter inserted into the lumen.
One method for delivery of therapeutic agent to the interior lumen walls is treatment of the balloon used in angioplasty procedures with therapeutic agent or therapeutic agent/polymer mixture such that when the balloon contacts the inner surface of the vascular lumen, the therapeutic agent is released into the adjacent tissue. Layered balloons with delivery ports for delivery of therapeutic agent through the ports to the inner surface of the lumen are known in the art, such as that disclosed in U.S. Pat. No. 5,843,089 to Sahatjian et al., which is expressly incorporated herein by reference.
Another method involves administering therapeutic agents systemically, e.g., orally or intravenously, to treat a restenosed site. In this case, a relatively large amount of the therapeutic agent must be administered so that, after being diluted during transport through the body, an effective dose reaches the site. Moreover, many parts of the body which are not diseased are still exposed to the therapeutic agent.
Another example of such procedures involves the use of stents. Stents are capable of maintaining intimate contact between a substance applied to the outer surface of the stent and the tissues of the vessel to be treated. Stents, however, can present challenges both with respect to securing a therapeutically significant amount of a substance on the stent during expansion of the stent into contact with the blood vessel wall, and also with respect to controlling the rate of drug delivery from the stent to the vessel wall.
U.S. Pat. No. 5,824,048 to Tuch describes an intravascular stent having a coating which includes a polymer and a therapeutic substance on the body of a stent, and in particular on its tissue-contacting surface, in which the coating has a greater concentration of therapeutic substance on the portion of the coating nearest the stent body than near the exterior surface of the coating. The inclusion of a polymer in intimate contact with a drug on the stent allows the drug to be retained on the stent in a resilient matrix during expansion of the stent and also slows the administration of the drug following implantation for improved application of therapeutic agent to the vessel.
U.S. Pat. No. 6,899,731 to Li et al., which is expressly incorporated herein by reference, discloses a method of delivering a negatively charged therapeutic agent to a target location within a mammalian body. The method comprises the steps of applying a multiplicity of alternating layers of at least one cationic polyelectrolyte carrier and a multiplicity of layers of a negatively charged therapeutic agent to at least one surface of an insertable medical device. The medical device is delivered to a target site within the body, and upon reaching the target site, the negatively charged therapeutic agent is released into the target site. The negatively charged therapeutic agent is disclosed as keeping therapeutic intact during the insertion and release stages.
Despite the advances in treatment of restenosis, it is desirable to provide better methods of delivery of therapeutic agent to a target location. Blood flow and particle interactions may diminish the volume and effectiveness of a therapeutic agent delivered to an occluded vessel through conventional procedures which employ stents, balloons, hydrogels and the like. Such inefficiencies lead to greater costs and more invasive procedures.